OBJECTIVE:We undertook a systems immunology approach of the adaptive immune system in multiple sclerosis (MS), overcoming tradeoffs between scale and level of detail, in order to identify the immunologic signature of MS and the changes wrought by current immunomodulatory treatments.
METHODS:We developed a comprehensive flow cytometry platform measuring 38 immunologic cell types in the peripheral blood of 245 individuals in a routine clinical setting. These include patients with MS, untreated or receiving any of 4 current immunomodulatory treatments (interferon-β, glatiramer acetate, natalizumab, or fingolimod), patients with autoimmune thyroid disease, and healthy controls.
RESULTS:An increase in memory CD8(+) T cells and B cells was observed in untreated patients with MS. Interferon-β and fingolimod induce significant changes upon multiple aspects of the peripheral immune system, with an unexpectedly prominent alteration of B cells. Overall, both treatments push the immune system in different directions, with only 2 significant effects shared across these treatments-an increase in transitional B cells and a decrease in class-switched B cells. We further identified heightened B cell-activating factor (BAFF) levels as regulating this shared B cell pathway.
CONCLUSIONS: A systems immunology approach established different immunologic profiles induced by current immunomodulatory MS treatments, offering perspectives for personalized medicine. Pathways shared between the immunologic architecture of existing efficacious treatments identify targets for future treatment design.
It is perhaps obvious, when you know what you are looking for. Look at panel B. Memory B cells. We have suggested that memory B cells are an important target for immunotherapy. It reproduces what we said yesterday.
Glaterimer is not so good, beta interferon is not much better and fingolimod is much more active…sound familiar in terms of efficacy. Natalizumab is good the other way as it blocks cells escaping from blood to CNS.
Furthermore treatment with GA, IFNbeta and fingo increase BAFF (B cell activating factor which is inversely related to memory B cell numbers.
With GA, BAFF levels are increased but it is variable as it is with beta interferon and even more increased with fingolimod.
Maybe this is the last of Glaterimer “mechanism of the week” I need to mention.
Someone said these posts are simply publicity for GA.
Now you know how it works?
Let them disprove the idea:-).